Pathogenesis and prevention of necrotizing enterocolitis.

Centre for Reviews and Dissemination, Hull York Medical School, University of York, Heslington, York, UK.
Current Opinion in Infectious Diseases (Impact Factor: 5.03). 03/2011; 24(3):183-9. DOI: 10.1097/QCO.0b013e328345d5b5
Source: PubMed

ABSTRACT Necrotizing enterocolitis (NEC) remains the most common serious acquired gastrointestinal disorder affecting preterm infants. Here we review recent advances in our understanding of the pathogenesis of this multifactorial condition and consider the implications for practice and research.
NEC is an important cause of mortality and serious morbidity in preterm infants. The risk is inversely proportional to gestational age and weight at birth. Fetal growth restriction and compromise may be additional specific risk factors. NEC, particularly severe NEC requiring surgical intervention and NEC with invasive infection, is associated with acute morbidity and mortality and adverse neurodevelopmental outcomes. The principal modifiable postnatal risk factors for NEC in preterm infants relate to enteral feeding practices including formula milk feeding, early and rapid advancement of enteral feed volumes, and exposure to H2-receptor antagonists.
Our understanding of the pathogenesis of this condition remains incomplete. With the exception of feeding with human milk, only limited evidence is currently available to support interventions to prevent NEC. Promising strategies that merit further evaluation in randomized controlled trials include the use of prebiotics and probiotics and the avoidance of exposure to H2-receptor antagonists.

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    ABSTRACT: Necrotizing enterocolitis (NEC) has largely been present in neonatal intensive care units for the past 60 years. NEC prevalence has corresponded with the continued development and sophistication of neonatal intensive care. Despite major efforts towards its eradication, NEC has persisted and appears to be increasing in some centers. The pathophysiology of this disease remains poorly understood. Several issues have hampered our quest to develop a better understanding of this disease. These include the fact that what we have historically termed 'NEC' appears to be several different diseases. Animal models that are commonly used to study NEC pathophysiology and treatment do not directly reflect the most common form of the disease seen in human infants. The pathophysiology appears to be multifactorial, reflecting several different pathways to intestinal necrosis with different inciting factors. Spontaneous intestinal perforations, ischemic bowel disease secondary to cardiac anomalies as well as other entities that are clearly different from the most common form of NEC seen in preterm infants have been put into the same database. Here I describe some of the different forms of what has been called NEC and make some comments on its pathophysiology, where available studies suggest involvement of genetic factors, intestinal immaturity, hemodynamic instability, inflammation and a dysbiotic microbial ecology. Currently utilized approaches for the diagnosis of NEC are presented and innovative technologies for the development of diagnostic and predictive biomarkers are described. Predictions for future strategies are also discussed. © 2014 S. Karger AG, Basel.
    Neonatology 08/2014; 106(4):289-295. DOI:10.1159/000365130 · 2.37 Impact Factor
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    ABSTRACT: Necrotizing enterocolitis (NEC) continues to be the most severe gastrointestinal emergency facing the preterm neonate. The pathogenesis of NEC is still a complex and poorly understood process, but with increasing understanding of the role of enteral feeding, gut immunity and the altered gut microbiota, new opportunities to reduce overall NEC rates are now possible. Prevention strategies continue to lead as the most suitable approaches to reducing NEC, as early diagnosis and rapid effective treatment of NEC are still not optimal. Programmatic changes are equally important as subscribing to individual prevention strategies. The primary focus of this review is to summarize the best strategies we currently have to eliminate NEC within an institution.
    Seminars in Fetal and Neonatal Medicine 11/2013; DOI:10.1016/j.siny.2013.10.001 · 3.13 Impact Factor
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    ABSTRACT: Objective Endogenous digoxin-like factor (EDLF) has been linked to vasoconstriction, altered membrane transport, and apoptosis. Our objective was to determine whether increased EDLF in the cord sera of preterm infants was associated with an increased incidence of necrotizing enterocolitis (NEC). Study Design Cord sera from pregnant women enrolled in a randomized trial of MgSO4 for fetal neuroprotection were analyzed for EDLF using a red cell Rb+ uptake assay in which the inhibition of sodium pump-mediated Rb+ transport was used as a functional assay of EDLF. Specimens were assayed blinded to neonatal outcome. Cases (NEC, n = 25) and controls (neonates not developing stage 2 or 3 NEC, n = 24) were matched by study center and gestational age. None of the women had preeclampsia. Cases and controls were compared using the Wilcoxon test for continuous and the Fisher exact test for categorical variables. A conditional logistic regression analysis was used to assess the odds of case vs control by EDLF level. Results Cases and controls were not significantly different for gestational age, race, maternal steroid use, premature rupture of membranes, or MgSO4 treatment. In logistic models adjusted for treatment group, race, premature rupture of membranes, and gestational age, cord sera EDLF was significantly associated with development of NEC (P = .023). Conclusion These data demonstrated an association between cord sera EDLF and NEC.
    American journal of obstetrics and gynecology 01/2013; 210(4). DOI:10.1016/j.ajog.2013.11.011 · 3.97 Impact Factor


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May 24, 2014